title: 3D QSAR CoMFA/CoMSIA, molecular docking and molecular dynamics studies of fullerene-based HIV-1 PR inhibitors.
abstract: For the first time, a set of experimentally reported [60] fullerene derivatives were subjected to the 3D-QSAR/CoMFA and CoMSIA studies. The aim of this study is to propose a series of novel [60] fullerene-based inhibitors with optimal binding affinity for the HIV-1 PR enzyme. The position of the template molecule at the cavity of HIV-1 PR was optimized and 3D QSAR models were developed. Relative contributions of steric/electrostatic fields of the 3D-QSAR/CoMFA and CoMSIA models have shown that steric effects govern the bioactivity of the compounds, but electrostatic interactions play also an important role.The de novo drug design Leapfrog simulations provided a series of novel compounds with predicted improved inhibition effect.
authors.affiliation: Institute of Organic and Pharmaceutical Chemistry, The National Hellenic Research Foundation, Vas. Constantinou Ave. 48, 11635 Athens, Greece. durdagis@eie.gr
authors.forename: Serdar
authors.initials: S
authors.lastname: Durdagi
authors.forename: Thomas
authors.initials: T
authors.lastname: Mavromoustakos
authors.forename: Manthos G
authors.initials: MG
authors.lastname: Papadopoulos
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D001665:Binding Sites; D003198:Computer Simulation; D037741:Fullerenes / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology*; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D019380:Anti-HIV Agents; D037741:Fullerenes; D016282:Aspartic Acid Endopeptidases